The goals of this proposal are: 1) to determine whether oral feeding of killed group A streptococci or their components to mice will induce resistance to upper respiratory infection, and 2) to elucidate the mechanism(s) of resistance. The success of this approach is suggested by studies of experimental dental caries in rats. These investigations have documented that feeding of killed Streptococcus mutans results in the appearance of specific secretory IgA in saliva and in protection against the development of caries after challenge with living organisms. Epizootic strains of group A streptococci, known to produce cervical lymphadenitis in mice under natural conditions, will be used to develop a mouse model. The immunizing and protective effects of feeding killed group A streptococci will be examined in this model. Level of IgA, IgG, and IgM and of specific streptococcal antibodies will be determined in saliva before and after oral and (sham) immunization and will be correlated with evidence of protection against challenge with living streptococci of homologous and heterologous types and groups. The adherence of group A streptococci will be compared in epithelial cells from immunized and non-immunized mice. The ability of saliva from immunized and non-immunized animals to prevent adherence will also be compared. If, as in the rat caries model, evidence of induced local resistance and of systemic immunosuppression is obtained, the mechanism(s) of these responses will be explored.